Tofacitinib alleviated salivary gland inflammation and reduced the percentages of effector T cells in murine Sjögren's disease

Abstract

Objective The Janus kinases-signal transducer and activator of transcription (JAK-STAT) signalling pathway plays a crucial role in autoimmunity and the signalling pathways of many cytokines in Sjögren's disease (SjD). Therefore, the aim of this study was to investigate both the therapeutic and immunomodulatory effects of the oral JAK3/JAK2/JAK1 inhibitor tofacitinib in a murine model of SjD. Methods Tofacitinib or vehicle was administered orally to the mice with SjD for 6weeks. Salivary flow rate was measured every three weeks. Pathological changes of salivary gland were detected by haematoxylin-eosin staining, and the percentages of subsets of CD4+ T cells and B cells in the cervical lymph nodes (cLNs) and spleen was determined by flow cytometry. Results Tofacitinib significantly ameliorated submandibular gland inflammation compared to the control group, as evidenced by reduced lymphocytic infiltration. Salivary flow rates improved significantly in tofacitinib treated mice compared to controls, indicating restored salivary gland function. The treatment also led to a substantial decrease in follicular helper T (Tfh) cells and the Tfh/Treg ratio in both the spleen and cLNs. Additionally, the frequencies of T helper 1 (Th1) and T helper 17 (Th17) cells were reduced in the spleen and cLNs. Conclusion Our data indicated that tofacitinib reduced percentages of effector T cells in an animal model of SjD. In addition, tofacitinib alleviated salivary gland inflammation and hypofunction, offering new insights into the clinical management of SjD.